Lung Cancer Vaccine to be Evaluated at Siteman Cancer Center

Gwen Ericson

Dec. 9, 2008 – A vaccine designed to prevent the recurrence of lung cancer is now being tested in centers around the world, including the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The vaccine stimulates the immune system to destroy cells that carry a tumor-specific antigen called MAGE-A3. This antigen is not present in normal tissue but is found in several cancer types, including 35 percent to 50 percent of cases of the most common type of lung cancer, non-small cell lung cancer.

The MAGE-A3-based vaccine answers a need for a highly efficient and safe therapy for patients who have undergone conventional treatment for a primary tumor but are at a high risk of relapse.

"The vaccine takes advantage of the immune system's built-in ability to eliminate foreign materials and harmful cells," says Bryan Meyers, MD, chief of thoracic surgery at Washington University. "This natural process has few side effects, unlike traditional treatments such as chemotherapy or radiation therapy."

Known as the MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell Lung Cancer Immunotherapy) trial, the study will test the vaccine to determine whether it can prolong survival by delaying or preventing recurrence of lung cancer. The study involves more than 400 centers in 33 countries, and study leaders hope to enroll 2,270 patients.

It is estimated that 215,000 men and women in the United States will be diagnosed with lung cancer in 2008. In people with lung cancer, the rate of recurrence and death is high, making the five-year survival rate only about 10 percent.

The trial is open to people with stage IB, II or IIIA non-small cell lung cancer with MAGE-A3-positive tumors. Participants must have undergone complete surgical removal of their tumors within six weeks of beginning the trial.

Meyers heads the MAGRIT trial at Washington University. "This trial is one of the few that focuses on patients with less-advanced lung cancer," he says. "Because lung cancer has few symptoms until later stages, most lung cancer patients we see have late-stage cancer – stage IIIB or IV – so the majority of lung cancer trials are designed for these patients."

The vaccine contains MAGE-A3 antigen particles along with compounds that cause inflammation. The inflammation helps alert the immune system to the antigen and activate killer T-cells that can eradicate cells with the antigen on their surface. Only cancer cells have the antigen.

Preliminary results in small trials have suggested that the vaccine does improve survival, but more data are needed to firmly establish its effectiveness. "With the MAGRIT trial, there will be a sufficient number of participants to give a definitive answer about which lung cancer patients will benefit from the vaccine and the degree of benefit," Meyers says.

Patients will be randomly assigned to receive 13 injections of either vaccine or an inactive solution into the upper arm muscle over a period of 27 months. Study centers will follow participants with periodic exams (including X-rays or CT scans, blood tests and physical examinations) for five years to see whether lung cancer recurs.

Lung cancer patients with stage IB to IIIA tumors often receive chemotherapy following surgery to help put their cancer into remission. Participants in the MAGRIT trial can still undergo standard chemotherapy if it is deemed advisable by their physicians. The only difference will be that they will also receive vaccine or placebo injections.

It is anticipated that the side effects from the vaccine may be mild because the vaccine primes the immune system only against tumor antigens. Normal tissue should not be affected. Most patients who experienced side effects in early trials had mild pain at the injection site or fever, fatigue and generalized muscle pain. Patients who are older or not as physically fit should be able to tolerate the vaccine, according to Meyers.

Physicians and patients interested in the MAGRIT trial can call 877-251-6485.

The MAGRIT study is sponsored by GlaxoSmithKline. Meyers has no financial interest in GlaxoSmithKline.